Chapter 30: Amino Acid Degradation and the Urea Cycle Flashcards
What is a ketogenic amino acid?
Amino acid carbon skeleton converted to acetyl CoA or acetoacetate
What is a glucogenic amino acid?
- Carbon skeletons converted to pyruvate, alpha-ketoglutarate, succinyl-CoA, fumarate or oxaloacetate
- Amino acids finally converted to glucose through gluconeogenesis
Amino acids are first used to build new _____. Those not needed for that are catabolized to make use of their _____.
- New proteins
- Make use of their nitrogen and carbon skeletons
Amino acid degradation primarily occurs in the _____.
Liver
First step is often removal of the alpha-amino group to generate _____.
Ammonia
After generation of ammonia, the carbon chains are altered for entry into _____.
Central pathways of carbon metabolism
Amino acids are made of _____ and _____.
Amine group and carboxylic group
What are the 3 key reactions of disposal of amino acids nitrogen?
- Transamination reactions
- Deamination reactions
- Glutamine Synthesis
The exchange of the NH2 group with =O group on another molecule is considered to be…
Transamination
The first key reaction of disposal of amino groups results in the following reaction:
Amino acid + Keto acid –> Keto acid + Amino acid
- Transamination
- One becomes the other
What catalyzes the transfer of the alpha-amino group of aspartate to alpha-ketoglutarate?
Aspartate transaminase
There are only a few keto acid acceptors. What is the most used?
Alpha-ketoglutarate
The second key reaction of disposal of amino groups has two parts:
Deamination
-
Oxidative deamination - aerobic conditions
- Catalyzed by glutamate dehydrogenase
- Important in liver where it releases ammonia for urea synthesis
-
Hydrolytic deamination
- Catalyzed by glutaminase and asparaginase
The third key reaction of disposal amino groups:
Glutamine Synthetase
NH3 –> Glutamate –> Glutamine
Used as a carrier of ammonia in most tissue
Glutamine
Used as a carrier in muscles
Alanine
What is the 1st step in amino acid degradation?
Nitrogen removal
Some amino acids can be _____ deaminated.
Directly
Removal of ammonium from most amino acids involves two steps:
- Aminotransferases (transaminases) transfer amino groups from an amino acid to alpha-ketoglutarate to generate glutamate
- Glutamate dehydrogenase, a mitochondrial enzyme, releases NH4+ in the oxidative deamination of glutamate
Peripheral tissues transport nitrogen to the _____.
Liver
Nitrogen can also be transported as _____ formed from glutamate by glutamine synthetase
Glutamine
Ammonia is toxic and needs…
To be excreted
What happens to excess ammonia?
Urea Cycle
What three molecules come into the urea cycle?
Ammonia and CO2 and Aspartate
Functions as detoxification of ammonia (prevents hyperammonemia)
Urea Cycle
Overall Urea Cycle occurs in the _____
Liver
Urea Cycle takes CO2, NH3 and aspartate + the cost of _____ to produce…
Cost of 3 ATP
To produce Urea and Fumarate
Glutamate Dehydrogenase reaction
Glutamate + NADP+ –> alpha-ketoglutarate + NH3 + NADPH
Generation of NH3
CPS Reaction:
NH3 + HCO3- + 2 ATP is converted to Carbamyl Phosphate by Carbamyl Phosphate Synthetase
CPS I (Mitochondria) uses _____ which is important for _____.
Uses NH3 which is important for urea cycle
CPS II (Cytosol) uses _____ which is important for _____.
Uses glutamine which is important for pyrimidine biosynthesis
Bicarbonate is activated by _____ to form _____.
Activated by ATP to form carbonyl-P
Carbonyl-P is converted to _____.
Carbamate
Carbamate is phosphorylated by _____. Carbamate converts to _____.
By ATP
Converted to carbomoyl phosphate
Urea Cycle: Carbamoyl P + _____ –> _____ by _____.
Ornithine –> Citrulline by Ornithine transcarbamylase
Ornithine + Citrulline are considered _____ amino acids.
- Non-standard (not present in proteins)
- Carry ammonium group from cytosol to mitochondria or vice versa
What gets added from the cytosol to citrulline?
Aspartate
Citrulline + Aspartate –> _____ by _____.
Argininosuccinate by Argininosuccinate synthetase
Elimination reaction leads to _____ and _____ (cytosol).
Arginine and fumarate
Argininosuccinate –> _____ by _____.
Arginine by Argininosuccinase (cytosol)
In the cytosol, arginine is converted to _____ by _____ which is transported into the _____.
Converted to Ornithine by Arginase (cytosol), which is transported into the mitochondria
Fumarate can be converted into _____ by the _____ and then into _____ by the _____.
Can be converted into oxaloacetate by the citric acid cycle and then into glucose by gluconeogenic pathway.
The urea cycle is generally controlled by _____
Substrate availability
The more ammonia, the higher the rate of _____.
Urea formation
Defects in any of the urea cycle enzymes results in elevated levels of _____ in the blood, which causes nervous system malfunction and can be lethal.
NH4+
Excessive alcohol consumption causes…
Liver cirrhosis
- Defects in catabolism of branched-chain amino acids
- Inability to degrade branched amino acids
Maple Syrup Urine Disease
Which amino acids can be directly deaminated to produce NH4+?
A. Serine and threonine B. Proline and valine C. Phenylalanine and tryptophan D. Glycine and alanine E. No amino acids can be directly deaminated
Serine and Threonine
Tryptophan is degraded to acetacetyl CoA and pyruvate, making it:
Both a ketogenic and glucogenic amino acid
Phenylketonuria is caused by a defect in:
A. Phenylalanine reductase B. Succinyl CoA synthetase C. Citrulline dehydrogenase D. Phenylalanine hydroxylase E. Tyrosine transaminase
Phenylalanine hydroxylase
Essential AAs generally..
Generally require higher amounts of energy for their synthesis than non-essential amino acids
Which serves a catalytic role in the urea cycle?
A. Carbamoyl phosphate B. Aspartate C. Ornithine D. Glutamate E. ATP
Ornithine
People with Maple Syrup Disease accumulate _____________ in their blood.
A. Leucine, isoleucine and valine
B. Homogentistic acid
C. Phenylalanine
D. Alpha-keto acids
E. Urea
Alpha-keto acids
Tyrosine can be broken down to fumarate and acetoacetate. Tyrosine is:
A. Solely a ketogenic amino acid B. Solely a glucogenic amino acid C. Both a ketogenic and a glucogenic amino acid D. Neither a ketogenic nor a glucogenic amino acid E. It is impossible to tell from this information
Both a ketogenic and a glucogenic amino acid
In mammals, nitrogen present in amino acids:
Comes primarily from dietary protein
Lysine is degraded through a series of steps to 2 Acetyl CoA + 2 CO2 molecules. Lysine is:
A. Solely a ketogenic amino acid B. Solely a glucogenic amino acid C. Both a ketogenic and a glucogenic amino acid D. Neither a ketogenic nor a glucogenic amino acid E. It is impossible to tell from this information
Solely a ketogenic amino acid
The two nitrogen atoms in urea are derived from __________ and ________.
Ammonia and aspartate
Nitrogen levels in the blood increase in the early stages of fasting because:
Amino acids become a major source for glucose production
Carbamoyl phosphate synthetase catalyzes synthesis of carbamoyl phosphate from NH3, ATP and:
A. Arginine B. Bicarbonate C. Urea D. Malonyl CoA E. Citrate
Bicarbonate
Which two compounds along with 2 ATP are used to make carbamoyl phosphate?
Bicarbonate and ammonia